Duality of Branched-Chain Amino Acids in Chronic Cardiovascular Disease: Potential Biomarkers versus Active Pathophysiological Promoters.

Branched-chain amino acids (BCAAs), comprising leucine (Leu), isoleucine (Ile), and valine (Val), are essential nutrients vital for protein synthesis and metabolic regulation via specialized signaling networks. Their association with cardiovascular diseases (CVDs) has become a focal point of scientific debate, with emerging evidence suggesting both beneficial and detrimental roles. This review aims to dissect the multifaceted relationship between BCAAs and cardiovascular health, exploring the molecular mechanisms and clinical implications. Elevated BCAA levels have also been linked to insulin resistance (IR), type 2 diabetes mellitus (T2DM), inflammation, and dyslipidemia, which are well-established risk factors for CVD. Central to these processes are key pathways such as mammalian target of rapamycin (mTOR) signaling, nuclear factor kappa-light-chain-enhancer of activate B cells (NF-κB)-mediated inflammation, and oxidative stress. Additionally, the interplay between BCAA metabolism and gut microbiota, particularly the production of metabolites like trimethylamine-N-oxide (TMAO), adds another layer of complexity. Contrarily, some studies propose that BCAAs may have cardioprotective effects under certain conditions, contributing to muscle maintenance and metabolic health. This review critically evaluates the evidence, addressing the biological basis and signal transduction mechanism, and also discusses the potential for BCAAs to act as biomarkers versus active mediators of cardiovascular pathology. By presenting a balanced analysis, this review seeks to clarify the contentious roles of BCAAs in CVD, providing a foundation for future research and therapeutic strategies required because of the rising prevalence, incidence, and total burden of CVDs.

The Usefulness of Nanotechnology in Improving the Prognosis of Lung Cancer.

Lung cancer remains a major public health problem both in terms of incidence and specific mortality despite recent developments in terms of prevention, such as smoking reduction policies and clinical management advances. Better lung cancer prognosis could be achieved by early and accurate diagnosis and improved therapeutic interventions. Nanotechnology is a dynamic and fast-developing field; various medical applications have been developed and deployed, and more exist as proofs of concepts or experimental models. We aim to summarize current knowledge relevant to the use of nanotechnology in lung cancer management. Starting from the chemical structure-based classification of nanoparticles, we identify and review various practical implementations roughly organized as diagnostic or therapeutic in scope, ranging from innovative contrast agents to targeted drug carriers. Available data are presented starting with standards of practice and moving to highly experimental methods and proofs of concept; particularities, advantages, limits and future directions are explored, focusing on the potential impact on lung cancer clinical prognosis.

Oxidative Stress and NRF2/KEAP1/ARE Pathway in Diabetic Kidney Disease (DKD): New Perspectives.

Diabetes mellitus (DM) is one of the most debilitating chronic diseases worldwide, with increased prevalence and incidence. In addition to its macrovascular damage, through its microvascular complications, such as Diabetic Kidney Disease (DKD), DM further compounds the quality of life of these patients. Considering DKD is the main cause of end-stage renal disease (ESRD) in developed countries, extensive research is currently investigating the matrix of DKD pathophysiology. Hyperglycemia, inflammation and oxidative stress (OS) are the main mechanisms behind this disease. By generating pro-inflammatory factors (e.g., IL-1,6,18, TNF-α, TGF-ß, NF-κB, MCP-1, VCAM-1, ICAM-1) and the activation of diverse pathways (e.g., PKC, ROCK, AGE/RAGE, JAK-STAT), they promote a pro-oxidant state with impairment of the antioxidant system (NRF2/KEAP1/ARE pathway) and, finally, alterations in the renal filtration unit. Hitherto, a wide spectrum of pre-clinical and clinical studies shows the beneficial use of NRF2-inducing strategies, such as NRF2 activators (e.g., Bardoxolone methyl, Curcumin, Sulforaphane and their analogues), and other natural compounds with antioxidant properties in DKD treatment. However, limitations regarding the lack of larger clinical trials, solubility or delivery hamper their implementation for clinical use. Therefore, in this review, we will discuss DKD mechanisms, especially oxidative stress (OS) and NRF2/KEAP1/ARE involvement, while highlighting the potential of therapeutic approaches that target DKD via OS.

Correlation between Carbonic Anhydrase Isozymes and the Evolution of Myocardial Infarction in Diabetic Patients.

(1) Background: Myocardial infarction was, until recently, recognized as a major coronary event, often fatal, with major implications for survivors. According to some authors, diabetes mellitus is an important atherogenic risk factor with cardiac determinations underlying the definition of the so-called "diabetic heart". The present study aims to establish a correlation between the evolution of myocardial infarction in diabetic patients, by determining whether lactic acid levels, the activity of carbonic anhydrase isoenzymes, and the magnitude of ST-segment elevation are correlated with the subsequent evolution of myocardial infarction. (2) Methods: The study analyzed 2 groups of 30 patients each: group 1 consisted of diabetic patients with acute myocardial infarction, and group 2 consisted of non-diabetic patients with acute myocardial infarction. Patients were examined clinically and paraclinical, their heart markers, lactic acid, and the activity of carbonic anhydrase I and II isozymes were determined. All patients underwent electrocardiogram and echocardiography analyses. (3) Results: The results showed that diabetics develop acute myocardial infarction more frequently, regardless of how much time has passed since the diagnosis. The value of myocardial necrosis enzymes was higher in diabetics than in non-diabetics, and acute coronary syndrome occurs mainly in diabetics with poor metabolic balance. Lethality rates in non-diabetic patients with lactic acid values above normal are lower than in diabetics. (4) Conclusions: Lactic acid correlated with the activity of isozyme I of carbonic dioxide which could be early markers of the prognosis and evolution of diabetic patients with acute myocardial infarction.

Antiepileptic Drugs and Their Dual Mechanism of Action on Carbonic Anhydrase.

(1) Background: The benefit of using inhibitors of carbonic anhydrase (CA), such as acetazolamide, in the treatment of epilepsy has previously been described. (2) Methods: In this paper, the effect on CA of the most well-known antiepileptic drugs was studied in vitro and in vivo. The effects, after chronic treatment, of carbamazepine, phenytoin, valproate, primidone, clonazepam, and ethosuximide were studied in vitro on purified CA, isozyme I (CA I) and CA, and isozyme II (CA II) activity and in vivo on epileptic erythrocyte CA I and CA II activity. (3) Results: In vitro results showed that all antiepileptic drugs reduced purified CA II activity according to dose-response relationships and slightly inhibited CA I activity. In vivo results showed that the chronic administration of antiseizure drugs induced a progressive reduction in erythrocyte CA II activity in all the groups studied. This study shows that CA II inhibition can be induced both in vitro and in vivo by major antiepileptic agents as it might be one of the effective mechanisms of these anticonvulsant drugs. (4) Conclusions: The decrease in CA II activity in epileptic patients after antiseizure treatment suggests the involvement of CA II in the pathogenesis of epilepsy.

Immune Thrombocytopenic Purpura as a Hemorrhagic Versus Thrombotic Disease: An Updated Insight into Pathophysiological Mechanisms.

Immune thrombocytopenic purpura (ITP) is a blood disorder characterized by a low platelet count of (less than 100 × 109/L). ITP is an organ-specific autoimmune disease in which the platelets and their precursors become targets of a dysfunctional immune system. This interaction leads to a decrease in platelet number and, subsequently, to a bleeding disorder that can become clinically significant with hemorrhages in skin, on the mucous membrane, or even intracranial hemorrhagic events. If ITP was initially considered a hemorrhagic disease, more recent studies suggest that ITP has an increased risk of thrombosis. In this review, we provide current insights into the primary ITP physiopathology and their consequences, with special consideration on hemorrhagic and thrombotic events. The autoimmune response in ITP involves both the innate and adaptive immune systems, comprising both humoral and cell-mediated immune responses. Thrombosis in ITP is related to the pathophysiology of the disease (young hyperactive platelets, platelets microparticles, rebalanced hemostasis, complement activation, endothelial activation, antiphospholipid antibodies, and inhibition of natural anticoagulants), ITP treatment, and other comorbidities that altogether contribute to the occurrence of thrombosis. Physicians need to be vigilant in the early diagnosis of thrombotic events and then institute proper treatment (antiaggregant, anticoagulant) along with ITP-targeted therapy. In this review, we provide current insights into the primary ITP physiopathology and their consequences, with special consideration on hemorrhagic and thrombotic events. The accumulated evidence has identified multiple pathophysiological mechanisms with specific genetic predispositions, particularly associated with environmental conditions.

Vitamin D Deficiency in Both Oral and Systemic Manifestations in SARS-CoV-2 Infection: Updated Review.

The specialized literature emphasizes the fact that vitamin D has a potentially beneficial effect in the context of the current COVID-19 pandemic. The purpose of this article is to highlight the role of vitamin D, both prophylactic and curative, in the treatment of patients diagnosed with COVID-19. Even though its relevance is still unknown and causes various controversies, there is currently no specific treatment for patients diagnosed with COVID-19. There are various prevention strategies with new vaccination schedules, but additional randomized and clinical trials are still needed to combat this pandemic. In addition to the systemic manifestations of SARS-CoV-2 infection, oral manifestations of this disease have also been described in the literature. The etiology of oral manifestations associated with COVID-19 infection and vitamin D deficiency remains controversial. In the present studies, oral manifestations such as salivary gland infections, aphthae, erythema, gingivitis, ulcers, etc. have been reported. This is a new topic, and the prevalence of manifestations is described in only a few studies, which is inconsistent with the number of COVID-19 cases reported since the beginning of the pandemic. The clinical symptomatology in patients with current COVID-19 infection is polymorphic. Whether the oral manifestation is directly caused by SARS-CoV-2 or a secondary manifestation remains an important topic to analyze and discuss.

The Pulmonary Venous Return from Normal to Pathological-Clinical Correlations and Review of Literature.

Pulmonary veins carry oxygenated blood from lungs to the left atrium of the heart. The anatomy of the pulmonary veins is variable with some anatomic variants. In clinical practice the difference between the normal anatomy of pulmonary veins with its variants and abnormal anatomy is very important for clinicians. Variants of pulmonary veins may occur in number, diameter and normal venous return. We present a case report and a review of the literature with the pulmonary venous return that deviates from the usual anatomical configuration and ranges from normal variant drainage to anomalous pulmonary-systemic communication. Initially, it was considered as an anatomical variant of the pulmonary venous return associated with the persistence of the left superior vena cava. Upon detailed exploration it was established that it was an anomaly of the pulmonary venous return which led in time to the installation of its complications. Diagnosis can be difficult, sometimes missed, or only made late in adulthood when complications were installed. Knowledge of variant anatomy and anomalous pulmonary venous return play a crucial role in the diagnostically challenging patient.

Role of Gut Microbiota on Onset and Progression of Microvascular Complications of Type 2 Diabetes (T2DM).

Type 2 diabetes mellitus (T2DM) remains one of the most problematic and economic consumer disorders worldwide, with growing prevalence and incidence. Over the last years, substantial research has highlighted the intricate relationship among gut microbiota, dysbiosis and metabolic syndromes development. Changes in the gut microbiome composition lead to an imbalanced gastrointestinal habitat which promotes abnormal production of metabolites, inflammatory status, glucose metabolism alteration and even insulin resistance (IR). Short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO), lipopolysaccharide, aromatic amino acids and their affiliated metabolites, contribute to T2DM via different metabolic and immunologic pathways. In this narrative review, we discuss the immunopathogenic mechanism behind gut dysbiosis, T2DM development and the major known diabetic microvascular complications (retinopathy, neuropathy and nephropathy), the beneficial use of pre- and pro-biotics and fecal microbiota transplantation in T2DM management and new findings and future perspectives in this field.

Chronometric vs. Structural Hypercoagulability.

Prolonged tourniquet stasis induced by venepuncture can lead to the release of the plasma of cell lysis products, as well as tissue factor (TF), impairing the quality of coagulation test results. The accidental presence of TF in vitro can trigger the coagulation mechanism, generating a false decrease in prothrombin time (PT). Background and Objectives: Identification of short PT tests below the normal reference value that could suggest a situation of hypercoagulability. The study aimed to compare the results of the shortened PT tests at their first determination with the eventual correction following duplication of the analysis from the same sample. Materials and methods: Identification of the shortened PT tests has been carried out for a period of 4 months, upon 544 coagulation samples referred to the Hematology department of Sf. Spiridon County Clinical Emergency Hospital from Iasi, Romania. Results: Out of the 544 samples of which the results indicated a state of hypercoagulability, by repeating the determination from the same sample, for 200 (36.76%) PT tests (p = 0.001) the value was corrected, falling within the normal reference range. For 344 (63.24%) tests, the results suggested a situation of hypercoagulability. Conclusions: In order to guarantee the highest quality of the laboratory services, a proper interpretation and report of the patients' results must be congruent and harmoniously associated to the actual clinical condition of the patient. Duplication of the PT determination from the same sample would exclude situations of false hypercoagulability and would provide significant improvement for the patient's safety.

Hypothyroidism-Induced Nonalcoholic Fatty Liver Disease (HIN): Mechanisms and Emerging Therapeutic Options.

Nonalcoholic fatty liver disease (NAFLD) is an emerging worldwide problem and its association with other metabolic pathologies has been one of the main research topics in the last decade. The aim of this review article is to provide an up-to-date correlation between hypothyroidism and NAFLD. We followed evidence regarding epidemiological impact, immunopathogenesis, thyroid hormone-liver axis, lipid and cholesterol metabolism, insulin resistance, oxidative stress, and inflammation. After evaluating the influence of thyroid hormone imbalance on liver structure and function, the latest studies have focused on developing new therapeutic strategies. Thyroid hormones (THs) along with their metabolites and thyroid hormone receptor ß (THR-ß) agonist are the main therapeutic targets. Other liver specific analogs and alternative treatments have been tested in the last few years as potential NAFLD therapy. Finally, we concluded that further research is necessary as well as the need for an extensive evaluation of thyroid function in NAFLD/NASH patients, aiming for better management and outcome.

Acute coronary syndrome with ST segment elevation in a patient with Addison disease: Case report and brief review of physiopathological mechanisms: A case study.

The adrenal gland serve important roles in the modulation of the immune response, the adjustment of blood pressure, the stress reaction via glucocorticoids and the hydroelectrolytic balance via mineralocorticoids. Primary adrenal insufficiency, known as Addison disease, is characterized by a decrease in glucocorticoid secretion (cortisol) and, more rarely, by a hyposecretion of mineralocorticoids (aldosterone). The production of cortisol, which is a hormone that helps the body respond to stress, is regulated in the brain, the hypothalamus and the pituitary gland. The hypothalamus stimulates the pituitary gland to produce adrenocorticotropic hormone, which stimulates cortisol production from the adrenal gland. If left untreated, Addison disease has a high mortality rate. Corticotherapy used in the treatment of Addison disease is associated with a certain cardiovascular risk. The proatherogenic effect of corticoids is based on the chronic inflammatory response of the vascular wall to a series of events. The aim of the current case report was to review the pathophysiological mechanisms and interactions that may lead to the onset of acute coronary syndrome with ST elevation in a patient with Addison disease.

Polymorphism of clinical manifestation of HPV infection in the genital mucosa - 3-year retrospective study.

BACKGROUND: Human papillomaviruses (HPVs) are associated with a wide variety of cutaneous and mucosal infections and with malignancies in humans. More than 100 HPV types have been identified, some of which have affinity for skin and others for mucosal sites. AIM: The purpose of this study came from our desire to support the "Stop Cervical Cancer" campaign, adopted as "Cervical Cancer Removed as a Public Health Problem", following the World Health Organization (WHO) initiative in 2019-2020. At European level, cervical cancer mortality has fallen by more than 30% over the past 30 years, through coherent, consistent and comprehensive prevention programs based on accurate and consistent public information. Romania is in an unfavorable situation with regard to incidence (32.8 new cases∕100 000 women) and cervical cancer mortality (10.9 deaths∕100 000 women). Free Babes-Papanicolau (Pap) testing for early detection of cervical cancer was valid this year until March. PATIENTS, MATERIALS AND METHODS: The study runs over a period of three years, between 2016-2018, in the "Elena Doamna" Hospital of Obstetrics and Gynecology, Iasi, Romania. Of the 8500 patients hospitalized for various diseases (ovarian cysts, uterine fibroids, endometriosis, abnormal vaginal bleeding, dysmenorrhea, ectopic pregnancies, placenta praevia, spontaneous abortions and on demand, benign, malignant tumors), only 382 were present in the ambulatory for Pap test. For the other conditions, Pap test denied because the patients did not want this but to solve the condition for which they presented themselves. RESULTS: We retrospectively review 382 Pap tests of patients who presented themselves in the Ambulatory Service of the Hospital both at the advice of the gynecologist and due to the program initiated by the WHO and supported by the Department of Public Health, Iasi: "Cervical cancer can be eliminated as a problem of public health". Lesions equal to or worse than high-grade squamous intraepithelial lesion (HSIL) equivalate with high-grade lesions including HSIL (cervical intraepithelial neoplasia - CIN1, CIN2). Endometrial lesions were excluded from the study. As seen of this campaign, the number of patients has increased in 2018 (242 cases), compared to 46 cases in 2017 and 94 cases in 2016. CONCLUSIONS: Our study demonstrated that 35% (7/20) of HSIL-confirmed biopsies previously had negative HPV assays. Despite the previous negative HPV tests, a wide variety of HPV genotypes has been detected in most biopsies. In our case, we frequently identified the HPV 59 and 45 strains, 51 cases with HSIL lesions presented a first positive HPV test, 13 cases with low-grade squamous intraepithelial lesion (LSIL) showed three negative HPV tests. Prevention plays an important role in reducing the incidence of cervical cancer cases. The Pap test is now considered the primary prevention method, but consecutive vaccination significantly increases protection against high-risk HPV strains. Education plays an important role in the prophylaxis of HPV infection and cancer. It should be instituted in schools, from puberty age through partnerships or government programs with public health directorates and university hospitals or using European funds.